Functional gastrointestinal disorders (FGIDs) are a group of gastrointestinal disorders not including organic diseases (colon cancer, ulcerative colitis, Crohn's disease, amebic dysentery, and such). FGIDs are caused by abnormalities of gastrointestinal functions such as motor and sensory functions, and develop various symptoms such as abdominal pain, nausea, vomiting, bloating sensation, and defecation trouble such as constipation and diarrhea, depending on the affected area.
FGIDs include a total of 25 diseases: six esophageal diseases, three gastroduodenal diseases, five intestinal diseases, two abdominal pains, two biliary tract diseases, three rectal/anal diseases, and four of the pediatric area. Of these, for example, diseases whose main symptom is constipation are the following two diseases, when the pediatric area is excluded: (constipation-type) irritable bowel syndrome (IBS) and functional constipation (FC).
FGIDs do not affect life prognosis. However, FGIDs reduce the quality of life (QOL) and increase medical expenses, and thus have a significantly unfavorable impact on the society.
In the last decades, significant advances have been made in the study of organic diseases, and even malignant tumors are no longer being called incurable diseases. On the other hand, studies on functional abnormalities of the gastrointestinal tract still remain immature. The prevalence of FGIDs is predicted to further increase in the 21st century which is called high-stress society. Thus, elucidation of the pathogenesis of FGIDs and the development of novel therapies are important objectives for the future.
Irritable bowel syndrome (IBS), which is included in FGIDs, is caused by functional abnormalities of the lower digestive tract, and its pathophysiology is known to be motility abnormalities of the intestines, mainly of the colon. The observed symptoms include abdominal pain, abdominal discomfort (characterized by being relieved by defecation), defecation abnormalities (diarrhea, constipation, and combination of diarrhea and constipation), abnormal stool form (inclusion of mucus and abnormal hardness), and sense of abdominal bloating. The intestinal transit time is shortened in the diarrhea type, while the time is prolonged in the constipation type. Although the area and contractile pattern differ, an enhanced intestinal motility state is observed in both types. It is reported that, as compared to healthy individuals, IBS patients show abnormal responses to stress, stimuli such as diet, and cholinergic agents. It is also known that the perception threshold to the rectal or ileocecum balloon distension is lower (Non-Patent Document 1).
Conventionally known agents for improving constipation symptoms include those that bloat the stool with water to improve the stool property and induce a desire to defecate (bulk-forming laxatives) and those that directly promote the intestinal movement, in particular, the intestinal contractile force (stimulant laxatives). Stimulant laxatives have a strong defecation effect; however, they are not suited for uses over a long period, because continued use results in tolerance. Furthermore, known methods for treating IBS include methods using anticholinergic agents to decrease abnormal intestinal spasms, methods using dietary fibers or the like to aid the movement of content by the effect of adjusting the stool water content and by a gelling effect, and methods using antianxiety agents to relieve the stress symptoms. However, many of the anticholinergic agents are designated as dangerous agents (e.g., Trancolon). Furthermore, polycarbophil calcium preparations which adjust the water content through gelling effect are contraindicated in patients with an acute abdominal disease, hypercalcemia, renal failure, nephrolithiasis, and such. Thus, the development of highly safe, novel preventive or therapeutic agents for functional gastrointestinal disorders has been expected.
Fermentation products by Propionibacterium freudenreichii are known as propionic acid bacteria fermentation products, and have been reported to be effective in the proliferation of various bifidobacteria, in the improvement of inflammatory bowel diseases, and such (Patent Document 1). Furthermore, 1,4-dihydroxy-2-naphthoic acid (DHNA), a component of fermentation products of propionic acid bacteria, has also been found to have the effect of promoting bifidobacterial proliferation (Patent Document 2), the effect of preventing and treating metabolic bone diseases (Patent Document 3), and the effect of alleviating the symptoms of abdominal discomfort of milk intolerance after milk ingestion (Patent Document 4).    [Patent Document 1] International publication WO 2005/099725 pamphlet.    [Patent Document 2] Japanese Patent Application Kokai Publication No. (JP-A) H08-98677 (unexamined, published Japanese patent application).    [Patent Document 3] International publication WO 01/28547 pamphlet.    [Patent Document 4] International publication WO 03/016544 pamphlet.    [Non-Patent Document 1] “Saishin Naikagaku Taikei, Progress 8, Shoukakan Shikkan (Latest Internal Medicine Outline, Progress 8, Gastrointestinal Diseases)”, Eds., Imura H. et al., pp. 51, 1997, Nakayama Shoten.